Washington Editor

The FDA said Neurochem Inc.'s Kiacta (eprodisate, formerly Fibrillex) is approvable for treating amyloid A (AA) amyloidosis, and the company's management is hopeful of clearing any final regulatory hurdles without additional trials.

Investors shared that optimism, as the Laval, Quebec-based firm's stock (NASDAQ:NRMX) jumped $2.23 Monday, or 23.5 percent, to close at $11.72.

"We are pleased with the decision," Lise Hébert, Neurochem's vice president of corporate communications, told BioWorld Today, "and we'll work with the agency to hopefully get an approval."

In its action letter, the FDA requested additional efficacy information and a safety update. The efficacy data "would probably" require one or more additional clinical trials, Neurochem Chairman, President and CEO Francesco Bellini said in a conference call, although he was more confident about an FDA-proposed alternative - that a further analysis from a complete follow-up of patients in an existing study "could be persuasive."

So the company plans to reevaluate patients from the double-blind study before it entered its open-label extension phase, especially those who dropped out.

That randomized, placebo-controlled trial enrolled 183 patients from 27 sites around the world. After a 24-month treatment period, 13.4 percent more Kiacta patients exhibited stabilized or improved kidney function (p=0.06), but to have met the primary endpoint, there should have been 20 percent more stabilized or improved patients in the Kiacta group vs. placebo (p=0.01).

Despite missing the primary endpoint, results demonstrated positive trends in that patient population, and a subsequent open-label extension study showed a reduction in the risk of renal decline or all-cause mortality to 41 percent relative to patients on placebo. (See BioWorld Today, April 19, 2005.)

Of the total number of patients enrolled in the single pivotal trial, 110 entered the open-label extension. About half had received Kiacta, and the remainder got placebo. With regard to the latter group, the so-called "delayed-treatment" patients, "the extension becomes very relevant" because of the time-to-event endpoint, Hébert said.

"For the FDA, hard endpoints on renal function are key in their assessment of the efficacy of Kiacta," she added, "so going back to the dropouts and adding information from the extension study should, we hope, provide reassurance on its efficacy."

Because the product's safety profile is "benign," Hébert said, "we simply have to provide an update." The FDA also requested further manufacturing and pharmacokinetic information, and acknowledged that a QT clinical study should be submitted as part of a post-approval commitment.

Neurochem already has begun collecting additional information for the FDA and expects to submit an amendment to its new drug application in the next four to six weeks. The company plans to request a 60-day review, so a decision could come before the end of the year.

Findings from the first year of the extension study were filed as part of a rolling submission that began a year ago, and further data from the second year of the open-label phase are to be included in this amendment. (See BioWorld Today, Aug. 23, 2005.)

"Really, the FDA is asking for an update up to the present," Hébert said, "and that's what we're doing."

Kiacta has orphan drug and fast-track status from the agency for AA amyloidosis, a progressive and fatal condition that occurs in some patients with chronic inflammatory disorders, chronic infections and inherited diseases such as familial Mediterranean fever. The oral compound, which works by preventing amyloid fibril formation, received a priority review from the FDA.

"There is a need for a treatment for the disease," Hébert said, "so Neurochem is committed to Kiacta."

The drug is partnered with Malvern, Pa.-based Centocor Inc., which has exclusive worldwide distribution rights, except for Canada, Switzerland, Japan, China, South Korea and Taiwan.

The partners are discussing the FDA's approvable letter, but Hébert said "it's too premature" to break down each company's cost burden should the program necessitate further studies.

Should any extra clinical work be required, a recently secured equity credit line for up to $60 million over the next two years would prove helpful. Neurochem's reserves stood at C$41.9 million (US$37.2 million) on June 30. (See BioWorld Today, Aug. 11, 2006.)

Neurochem plans to file for Kiacta's European approval next month.